Affiliation:
1. Department of Biological Chemistry, Johns Hopkins Medical School, Baltimore, MD 21205, USA.
Abstract
African trypanosomes, the cause of sleeping sickness, need massive amounts of myristate to remodel glycosyl phosphatidylinositol (GPI) anchors on their surface glycoproteins. However, it has been believed that the parasite is unable to synthesize any fatty acids, and myristate is not abundant in the hosts' bloodstreams. Thus, it has been unclear how trypanosomes meet their myristate requirement. Here we found that they could indeed synthesize fatty acids. The synthetic pathway was unique in that the major product, myristate, was preferentially incorporated into GPIs and not into other lipids. The antibiotic thiolactomycin inhibited myristate synthesis and killed the parasite, making this pathway a potential chemotherapeutic target.
Publisher
American Association for the Advancement of Science (AAAS)
Reference26 articles.
1. Ferguson M. A., Low M. G., Cross G. A., J. Biol. Chem. 260, 14547 (1985).
2. Masterson W. J., Raper J., Doering T. L., Hart G. W., Englund P. T., Cell 62, 73 (1990).
3. C. Edelstein in Biochemistry and Biology of Plasma Lipoproteins A. M. Scanu and A. A. Spector Eds. (Dekker New York 1986) pp. 495–505.
4. Dixon H., Ginger C. D., Williamson J., Comp. Biochem. Physiol. B 39, 247 (1971).
5. Werbovetz K. A., Englund P. T., Mol. Biochem. Parasitol. 85, 1 (1997).
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